Abstract
Liver X receptors (LXRα and LXRβ ) are oxysterol receptors that function as master transcription factors mediating cholesterol homeostasis in the periphery. LXRs regulate the levels of the ABCA1 and ABCG1 cholesterol transporters as well as apolipoproteins (apoE and apoC) in various cells thereby affecting cholesterol transport and metabolism. In the brain, LXRs regulate ABCA1 in both neurons and glia resulting in cholesterol efflux from these cells. In addition, the expression of apolipoprotein E (apoE), synthesized primarily by astrocytes and microglia, is also upregulated by LXR agonists. As both apoE and the ABCA1 transporter are intimately involved in amyloid-β peptide (Aβ ) transport and clearance, activation of these genes by LXR agonists in brain may have a significant impact on Aβ deposition and amyloid/ neuritic plaque formation. Furthermore, LXR activation has been shown to have significant anti-inflammatory properties. Taken together, these findings suggest that brain-penetrable LXR agonists or modulators may be useful therapeutic agents for the treatment and (or) prevention of Alzheimers disease.
Keywords: Nuclear hormone receptors, cholesterol, amyloid, ABCA1, apolipoprotein E, glia
Current Alzheimer Research
Title: Liver X Receptor-Mediated Gene Regulation and Cholesterol Homeostasis in Brain: Relevance to Alzheimers Disease Therapeutics
Volume: 4 Issue: 2
Author(s): Guoqing Cao, Kelly R. Bales, Ronald B. DeMattos and Steven M. Paul
Affiliation:
Keywords: Nuclear hormone receptors, cholesterol, amyloid, ABCA1, apolipoprotein E, glia
Abstract: Liver X receptors (LXRα and LXRβ ) are oxysterol receptors that function as master transcription factors mediating cholesterol homeostasis in the periphery. LXRs regulate the levels of the ABCA1 and ABCG1 cholesterol transporters as well as apolipoproteins (apoE and apoC) in various cells thereby affecting cholesterol transport and metabolism. In the brain, LXRs regulate ABCA1 in both neurons and glia resulting in cholesterol efflux from these cells. In addition, the expression of apolipoprotein E (apoE), synthesized primarily by astrocytes and microglia, is also upregulated by LXR agonists. As both apoE and the ABCA1 transporter are intimately involved in amyloid-β peptide (Aβ ) transport and clearance, activation of these genes by LXR agonists in brain may have a significant impact on Aβ deposition and amyloid/ neuritic plaque formation. Furthermore, LXR activation has been shown to have significant anti-inflammatory properties. Taken together, these findings suggest that brain-penetrable LXR agonists or modulators may be useful therapeutic agents for the treatment and (or) prevention of Alzheimers disease.
Export Options
About this article
Cite this article as:
Cao Guoqing, Bales R. Kelly, DeMattos B. Ronald and Paul M. Steven, Liver X Receptor-Mediated Gene Regulation and Cholesterol Homeostasis in Brain: Relevance to Alzheimers Disease Therapeutics, Current Alzheimer Research 2007; 4 (2) . https://dx.doi.org/10.2174/156720507780362173
DOI https://dx.doi.org/10.2174/156720507780362173 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
Call for Papers in Thematic Issues
New Advances in the Prevention, Diagnosis, Treatment, and Rehabilitation of Alzheimer's Disease
Aims and Scope: Introduction: Alzheimer's disease (AD) poses a significant global health challenge, with an increasing prevalence that demands concerted efforts to advance our understanding and strategies for prevention, diagnosis, treatment, and rehabilitation. This thematic issue aims to bring together cutting-edge research and innovative approaches from multidisciplinary perspectives to address ...read more
Current updates on the Role of Neuroinflammation in Neurodegenerative Disorders
Neuroinflammation is an invariable hallmark of chronic and acute neurodegenerative disorders and has long been considered a potential drug target for Alzheimer?s disease (AD) and dementia. Significant evidence of inflammatory processes as a feature of AD is provided by the presence of inflammatory markers in plasma, CSF and postmortem brain ...read more
Deep Learning for Advancing Alzheimer's Disease Research
Alzheimer's disease (AD) poses a significant global health challenge, with an increasing number of individuals affected yearly. Deep learning, a subfield of artificial intelligence, has shown immense potential in various domains, including healthcare. This thematic issue of Current Alzheimer Research explores the application of deep learning techniques in advancing our ...read more
Diagnostic and therapeutic biomarkers of dementia
Dementia affects 18 million people worldwide. Dementia is a syndrome of symptoms caused by brain disease, usually chronic or progressive, clinically characterized by multiple impairments of higher cortical functions such as memory, thinking, orientation, and learning. In addition, in the course of dementia, cognitive deficits are observed, which often hinder ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Conference Report: 8<sup>th</sup> Clinical Trials on Alzheimer Disease (CTAD), Barcelona, Spain November 5-7, 2015
CNS & Neurological Disorders - Drug Targets Acetylcholine Receptors and Tau Phosphorylation
Current Molecular Medicine Role of ARBs in the Blood Hypertension Therapy and Prevention of Cardiovascular Events
Current Drug Targets Generation and Transplantation of Dopaminergic Neurons Derived from Embryonic Stem Cells
Current Stem Cell Research & Therapy Cell Microencapsulation Implants into the Central Nervous System
Recent Patents on Nanomedicine From Physiome to Pathome: A Systems Biology Model of Major Depressive Disorder and the Psycho-Immune-Neuroendocrine Network
Current Psychiatry Reviews Mechanisms of Synaptic Homeostasis in Alzheimers Disease
Current Alzheimer Research Preface
Current Medicinal Chemistry - Immunology, Endocrine & Metabolic Agents Macrophage Derived Cystatin B/Cathepsin B in HIV Replication and Neuropathogenesis
Current HIV Research The Peripheral Nervous System and the Pathogenesis of Prion Diseases
Current Molecular Medicine Editorial - The As and Ms of Alzheimers Disease
Current Alzheimer Research Design, Synthesis and Biological Evaluation of Scutellarein Derivatives as Potential Anti-Alzheimers Disease Candidates Based on Metabolic Mechanism
Letters in Drug Design & Discovery Caring for HIV-Infected Patients in the ICU in The Highly Active Antiretroviral Therapy Era
Current HIV Research The Role of VE-cadherin in Blood-brain Barrier Integrity Under Central Nervous System Pathological Conditions
Current Neuropharmacology Epigenomic Approach in Understanding Alzheimer’s Disease and Type 2 Diabetes Mellitus
CNS & Neurological Disorders - Drug Targets Multidrug-Resistance (MDR) Proteins Develops Refractory Epilepsy Phenotype:Clinical and Experimental Evidences
Current Drug Therapy Modifiable Risk Factors Associated with Alzheimer’s Disease with Special Reference to Sleep Disturbance
CNS & Neurological Disorders - Drug Targets Molecular Evidence of Cryptotanshinone for Treatment and Prevention of Human Cancer
Anti-Cancer Agents in Medicinal Chemistry Therapeutic Potential of 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Inhibitors for the Treatment of Retinal and Eye Diseases
CNS & Neurological Disorders - Drug Targets Homocysteine and Cerebral Stroke in Developing Countries
Current Medicinal Chemistry